umbilical cord blood transplantation from unrelated donors

Conditions: Acute Leukemia; Immune Deficiency Disorder; Congenital Hematological Disorder; Metabolism Disorder; Aplastic Anemia; Myelodysplastic Syndromes; Chronic Leukemia; Lymphoma; Multiple Myeloma; Solid Tumor

Summary: this study is a single-center, treatment protocol with 4 possible preparative regimens, designed to validate the process of umbilical cord blood stem cell transplantation at our institution.

this study is a single-center treatment protocol with four possible preparative regimens, designed to validate the process of umbilical cord blood stem cell transplantation at our institution. enrolled patients will receive chemotherapy +/-total body radiation as a pre-transplant conditioning regimen. patients will then receive cord blood stem cells followed by gvhd prophylaxis that will include tacrolimus and mycophenolate mofetil, or cyclosporin a and methylprednisolone. multiple data points will be collected prior to, during, and following transplantation to ensure safety of the process and to evaluate the stated objectives.

Eligibility criteria:
inclusion criteria: * appropriate diagnosis: patients must have a disease or syndrome amenable to therapy with hematopoietic stem cell transplantation. diagnoses include, but are not limited to: * congenital and other non-malignant disorders: * immunodeficiency disorders (e.g. severe combined immunodeficiency, wiskott-aldrich syndrome) * congenital hematopoietic stem cell defects (e.g. chediak-higashi syndrome, congenital osteopetrosis, osteogenesis imperfecta) * metabolic disorders (e.g. hurler's syndrome) * severe aplastic anemia * high-risk leukemia: * acute myelogenous leukemia * refractory to standard induction therapy (more than 1 cycle required to achieve remission) * recurrent (in cr ≥ 2) * treatment-related aml or mds * evolved from myelodysplastic syndrome * presence of flt3 abnormalities * fab m6 or m7 * adverse cytogenetics * myelodysplastic syndrome * acute lymphoblastic leukemia including t lymphoblastic leukemia: * refractory to standard induction therapy (time to cr \>4 weeks) * recurrent (in cr ≥ 2) * wbc count \>30,000/mcl at diagnosis * age \>30 at diagnosis * adverse cytogenetics, such as t(9:22), t(1:19), t(4:11), and other mll rearrangements. * chronic myelogenous leukemia in accelerated phase or blast crisis * biphenotypic or undifferentiated leukemia * burkitt's leukemia or lymphoma * lymphoma: * large cell, mantle cell, hodgkin lymphoma refractory or recurrent, chemo-sensitive, and ineligible for an autologous stem cell transplant or previously treated with autologous sct * marginal zone or follicular lymphoma that is progressive after at least two prior therapies * multiple myeloma, recurrent following high-dose therapy and autologous sct or ineligible for an autologous hsct * solid tumors, with efficacy of allogeneic hsct demonstrated for the specific disease and disease status * adequate organ function: * cardiac - lvef \>45%, or shortening fraction \>25%, absence of congestive heart failure or conduction disturbances with high risk for sudden death * pulmonary - dlco (corrected for hemoglobin), fev1 and fvc ≥ 50% predicted; * renal - serum cr \< 1.5 times the upper limit of normal for age or gfr ≥ 50 ml/min/1.73m2 * hepatic - total bilirubin level \< 2 times the upper limit of normal (except for patients with gilbert's syndrome or hemolysis); if the primary disease process is causal, this criterion will be reconsidered. alt, ast, and alkaline phosphatase ≤ 5 times upper limit of normal. * performance status karnofsky or lansky score ≥ 70%. * informed consent must be obtained prior to initiating conditioning therapy. * receipt of viable cord blood product(s), single or dual, must be confirmed with the stem cell processing laboratory prior to initiating conditioning therapy. exclusion criteria: * availability of 10/10 or 9/10 hla-matched related or unrelated donor within a reasonable timeframe dictated by the clinical urgency of the transplant * autologous hsct \< 6 months prior to proposed ucb transplant * pregnant or breast feeding * current uncontrolled infection * evidence of hiv infection or positive hiv serology